October 19 Research Roundup: Dementia, Frankenstein Proteins, and Epigenetic Sperm Changes
There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.
Dementia may be caused by non-inherited DNA errors
Most researchers believe that only about one in 20 dementias are inherited. Researchers at the University of Cambridge published research in the journal Nature Communications that suggests spontaneous DNA mutations may cause the majority of dementias.
The research team studied 173 tissue samples from the Newcastle Brain Tissue Resource, part of the Medical Research Council (MRC)’s UK Brain Banks Network. The samples were from 54 people, 14 healthy, 20 with Alzheimer’s, 20 with Lewy body dementia. They sequenced 102 genes in brain cells over 5,000 times, including genes linked to common neurodegenerative diseases. They found spontaneous (somatic mutations) in 27 out of the 54 brains, including both healthy and diseased.
“These spelling errors arise in our DNA as cells divide, and could explain why so many people develop disease such as dementia when the individual has no family history,” stated Patrick Chinnery, who led the research. “These mutations likely form when our brain develops before birth—in other words, they sat there waiting to cause problems when we are older. Our discovery may also explain why no two cases of Alzheimer’s or Parkinson’s are the same. Errors in the DNA in different patterns of brain cells may manifest as subtly different symptoms.”
“Frankenstein proteins” used to heal tissue
Proteins are in constant motion. They fold. For quite some time, it was believed that proteins required a fixed shape to function, but over the last 20 years, research has suggested that that is not always the case, particularly for what are called intrinsically disordered proteins (IDPs). But the various forms the IDPs take aren’t random.
Biomedical engineers from Duke University and Washington University in St. Louis injected an artificial protein they developed from ordered and disordered segments, and they created a solid scaffold in response to body heat, which after a few weeks, integrated into tissue. It has the potential to be used in tissue engineering and regenerative medicine. The research was published in the journal Nature Materials.
These so-called “Frankenstein proteins” combined ordered and disordered regions, creating “partially ordered proteins” or POPs. “This material is very stable after injection,” stated Stefan Roberts, a PhD student in Ashutosh Chilkoti’s lab at Duke University and lead author of the study. “It doesn’t degrade quickly and it holds its volume really well, which is unusual for a protein-based material. Cells also thrive in the material, repopulating the tissue in the area where it is injected. All of these characteristics could make it a viable option for tissue engineering and wound healing.”
It Might Be Possible to Regrow Cells Related to Hearing Loss
Among life on earth, mammals are some of the only creatures that can’t regenerate damaged hearing. Birds, frogs, fish, they all have the ability to regenerate sensory hair cells after they’re damaged.
“It’s funny, but mammals are the oddballs in the animal kingdom when it comes to cochlear regeneration,” said Jingyuan Zhang, researcher with the University of Rochester Department of Biology, in a statement. “We’re the only vertebrates that can’t do it.” Zhang is the co-author of a recent study published in the European Journal of Neuroscience describing their efforts to regrow the sensory hair cells found in the cochlea.
Zhang and Patricia White, a research associate professor at the University of Rochester Medical Center (URMC) Del Monte Institute for Neuroscience, as well as researchers at the Massachusetts Ear and Eye Infirmary, part of Harvard Medical School, tested a theory that signaling from the EGF family of receptors participated in cochlear regeneration in mammals. They focused on ERBB2, a specific receptor found in cochlear support cells.
They used a variety of methods to activate the EGF signaling pathway, including a virus that targets ERBB2 receptors, and genetically modified mice that overexpressed an activated ERBB2, in addition to two drugs that were originally developed to stimulate stem cell activity in the eyes and pancreas.
White stated, “The process of repairing hearing is a complex problem and requires a series of cellular events. You have to regenerate sensory hair cells and these cells have to function properly and connect with the necessary network of neurons. This research demonstrates a signaling pathway that can be activated by different methods and could represent a new approach to cochlear regeneration and, ultimately, restoration of hearing.”
A Single Molecule Might Predict 2 Subtypes of Crohn’s Disease
Crohn’s disease, a chronic inflammatory condition of the intestinal tract, has been suspected of being a collection of related but slightly different diseases. As such, there are a lot of subtypes, but there’s been no way to predict which possible subtype a person may develop. But researchers at Cornell University and the University of North Carolina (UNC) have identified a single molecule, microRNA-31 (miR-31) that can predict subtype 1 or subtype 2 of Crohn’s disease. They published their work in the journal JCI Insight.
Subtype 1 patients don’t generally respond well to medications, and often develop extreme narrowing of the gut tube, requiring surgery. “We are not at the point at which we are able to perform personalized medicine on this, but at the very least we think it can lead to better clinical trial designs,” stated Praveen Sethupathy, associate professor in the Department of Biomedical Sciences at Cornell’s College of Veterinary Medicine and a senior co-author of the study, along with Terrence Furey, associate professor of Genetics and Shehzad Sheikh, associate professor of medicine, both at UNC.
Epigenetic Memory Transmitted Via Sperm
Increasingly, research is showing that changes in the genome, often epigenetic changes caused by trauma or health conditions, are passed down the generations. Some of this is via mitochondrial DNA, which is passed down in the female’s eggs. Now, researchers at the University of California, Santa Cruz (UCSC) have shown in animal models that these epigenetic changes caused by diet or environmental stress can be passed down in the sperm. Their research was published in the journal Nature Communications.
Conducting research on roundworms, Caenorhabditis elegans, found that epigenetic markers were transmitted from both sides to offspring, and that the information delivered by the sperm to the embryo is “both necessary and sufficient to guide proper development of germ cells in the offspring.”
Susan Strome, a distinguished professor of molecular, cell, and developmental biology at U of C – Santa Cruz, who led the research, stated, “We decided to look at C. elegans because it is such a good model for asking epigenetic questions using powerful genetic approaches.”
Epigenetic changes don’t affect the DNA sequences of genes, but modify the chemistry of the DNA itself or the histone proteins that package the DNA. These changes can cause genes to turn on or off at different times or in different cells. It was thought that sperm didn’t retain any of this histone packaging, but recent studies, including this one, have indicated that about 10 percent of histone packaging remains in both human and mouse sperm.
“Furthermore,” Strome stated, “where the chromosomes retain histone packaging of DNA is in developmentally important regions, so those findings raised awareness of the possibility that sperm may transmit important epigenetic information to embryos.”
“Vast Leukemia Dataset” Published
Scientists from the Howard Hughes Medical Institute and Oregon Health & Science University (OHSU) published a massive dataset that details the molecular makeup of more than 500 patients with acute myeloid leukemia (AML). An article about the work was published in the journal Nature.
The new research is initial data from the BeatAML program. Brian Druker, a Howard Hughes investigator at OHSU led the work with Jeffrey Tyner from OHSU. “People can get online, search our database, and very quickly get answers to ‘Is this a good drug?’ or ‘Is there a patient population my drug can work in?’” Druker stated.
Druker and Tyner worked with researchers at 11 academic medical centers and 11 biopharma companies. They collected and analyzed 672 samples of cancer cells from 562 patients. The data included complete DNA sequence of each sample’s protein-coding genes in addition to profiles of gene activity. They also evaluated how tumor cells from 409 of the samples responded to each of 122 different therapies.
“The real power comes when you start to integrate all that data,” Druker stated. “You can analyze what drug worked and why it worked.”